Body mass index, adiposity and tumour infiltrating lymphocytes as prognostic biomarkers in patients treated with immunotherapy: A multi-parametric analysis

• Published in: European journal of cancer (1990) Vol. 145; pp. 197 - 209
• Main Authors: Esposito, Angela, Marra, Antonio, Bagnardi, Vincenzo, Frassoni, Samuele, Morganti, Stefania, Viale, Giulia, Zagami, Paola, Varano, Gianluca M., Buccimazza, Giorgio, Orsi, Franco, Venetis, Konstantinos, Mazzarella, Luca, Viale, Giuseppe, Fusco, Nicola, Criscitiello, Carmen, Curigliano, Giuseppe
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.03.2021; Elsevier Science Ltd
• Subjects: Adipose tissue; Biomarkers; Body composition; Body mass; Body mass index; Body size; Body weight; Clinical trials; Computed tomography; Continuity (mathematics); Immune checkpoint inhibitors; Immune response; Immune system; Immunogenicity; Immunotherapy; Lymphocytes; Metastases; Overweight; Parametric analysis; Parametric statistics; Phase I; Solid tumors; Solid tumours; Survival; Tumors; Underweight; CTCAE; PR; PS; ICIs; Body composition; ORR; TFA; SFA; VFA; Body mass index; SD; CBR; Immunotherapy; ECOG; ULN; mABs; PD-L1; CTLA-4; PFS; BMI; NSCLC; OS; CI; TMB; Immune checkpoint inhibitors; CR; Phase I; PD; Solid tumours; Biomarkers; irAEs; TILs; PD-1
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2020.12.028

We performed a multi-parametric analysis investigating the association between adiposity (as measured using body mass index [BMI] and computed tomography [CT]-based body composition), tumour infiltrating lymphocytes (TILs) and clinical outcomes in patients with advanced-stage cancer treated with immunotherapy in phase I clinical trials. All consecutive patients (N = 153) with metastatic solid tumours treated within immunotherapy-based phase I clinical trials between August 2014 and May 2019 at our institution were included. Baseline characteristics, BMI, TILs value and CT-assessed fat indices (total fat area [TFA], subcutaneous fat area [SFA] and visceral fat [VFA]) were collected. The primary endpoints were to evaluate the impact of these parameters on overall survival (OS) and progression-free survival (PFS). Kaplan–Meier method and Cox proportional-hazards model were used for survival analyses. At both univariate and multivariate analyses, BMI was not associated with PFS neither when considered as continuous variable (HR 0.90, 95% CI 0.74–1.09, P = 0.28) nor as dichotomous variable (underweight/normal versus overweight/obese) (HR 0.79, 95% CI 0.55–1.14, P = 0.21). Interestingly, patients diagnosed with ‘immunogenic’ tumours and higher VFA/SFA ratio (1st and 2nd tertile versus 3rd tertile) presented an increased OS (HR 0.88, 95% CI 0.78–1.00, P = 0.047). Our analysis showed that patients with tumours that are already known as responsive to ICIs with higher VFA/SFA ratio presented an increased OS. Further studies are needed to elucidate the effect of adiposity on the host immune response to immunotherapy. •No association links adiposity and outcome in patients treated with immunotherapy.•Patients responsive to immunotherapy with a higher VFA/SFA ratio have a better OS.•The results of our analysis need to be confirmed in subsequent prospective studies.